Chap 20 Flashcards
Selective toxicity
selectively finding and destroying pathogens without damaging the host
Chemotherapy
the use of chemicals to treat a disease
Antibiotic
a substance produced by a microbe that, in small amounts, inhibits another microbe
Antimicrobial drugs
synthetic substances that interfere with the growth of microbes
1928: Fleming discovered penicillin, produced by
Penicillium
1932: Prontosil red dye used for
streptococcal infections
1940: First clinical trials of
penicillin
Today there is a growing problem of
antibiotic resistance
Bacillus subtilis
Bacitracin
Paenibacillus polymyxa
polymixin
More than half our antibiotics are produced by a certain genus of bacteria. What is it?
streptomyces
Narrow spectrum of microbial activity:
drugs that affect a narrow range of microbial types
Broad-spectrum antibiotics
affect a broad range of gram-positive or gram-negative bacteria
Superinfection
overgrowth of normal microbiota that is resistant to antibiotics
Identify at least one reason why it’s so difficult to target a pathogenic virus without damaging the host’s cells.
viruses replicate inside the host cell, utilizing the host’s own cellular machinery to multiply, meaning any attempt to disrupt the virus’s life cycle could also disrupt normal cellular functions, leading to host cell damage.
Bactericidal
Kill microbes directly
Bacteriostatic
Prevent microbes from growing
________ _________target certain essential functions of the microbe
antimicrobial drugs
Mechanisms of action include
1.inhibiting cell wall synthesis, 2.inhibiting protein synthesis,
3.inhibiting nucleic acid synthesis,
4. injuring the plasma membrane
5.inhibiting synthesis of essential metabolites
antimicrobial drug must not interfere with
essential functions of the microbe’s host
Penicillins prevent the synthesis of
peptidoglycan
Inhibiting protein synthesis
Target bacterial 70S ribosomes
Examples of drugs that inhibit protein synthesis
Chloramphenicol, erythromycin, streptomycin, tetracyclines
Injuring the plasma membrane
1.Polypeptide antibiotics change membrane permeability.
- Antifungal drugs combine with membrane sterols
- Ionophores antibiotics allow uncontrolled movement of cations (not for human use).
Inhibiting nucleic acid synthesis
Interfere with D N A replication and transcription
Inhibiting the synthesis of essential metabolites
Antimetabolites compete with normal substrates for an enzyme.
Sulfanilamide competes with
para-aminobenzoic acid (P A B A), stopping the synthesis of folic acid.
What cellular function is inhibited by tetracyclines?
protein synthesis
Chemotherapeutic Agents
antimicrobial drugs that fight disease by targeting a particular structural difference between human cells and those of the microbe
Why is it easier to develop antibacterial drugs?
Bacteria have many such differences
Viruses depend on the host’s machinery, so there are
fewer differences to target
eukaryotic pathogens such as ________& _________ have fewer differences from eukaryotic human cells
fungi & protozoa
eukaryotic pathogens such as fungi & protozoa have fewer differences from eukaryotic human cells, making it difficult to find drugs that have selective
toxicity against these pathogens.
treponema palladium
causes syphilis
Synthetic antibiotics vs natural antibiotics
natural- comes from another microbe to be used to fight against
synthetic- not found in nature
semisynthetic antimicrobial
chemically modified of a natural
antimicrobial drug
chemical substance that destroys pathogenic microorganisms with minimal damage to host tissues.
Chemotherapeutic agents include
chemicals that combat disease in the body.
developed the concept of chemotherapy to treat microbial diseases
Paul Ehrlich
came into prominence in the 1930s
sulfa drugs
discovered the first antibiotic, penicillin, in 1928; its first clinical trials were done in 1940.
Alexander Fleming
Most antibiotics are made by
Streptomyces bacteria
Antibacterial drugs affect many targets in a
prokaryotic cell.
Fungal, protozoan, and helminthic infections are more difficult to treat because
these organisms have eukaryotic cells.
Narrow-spectrum drugs affect only a select group of
microbes (gram-positive cells, for example);
broad-spectrum drugs
affect a more diverse range of microbes.
Which drugs can affect gram-negative cells?
Small, hydrophilic drugs
Antimicrobial agents should not cause excessive
harm to normal microbiota.
Superinfections occur when
1.a pathogen develops resistance to the drug being used
2.when normally resistant microbiota multiply excessively.
Antimicrobials generally act either by
directly killing microorganisms (bactericidal) or by inhibiting their growth (bacteriostatic).
Some agents, such as penicillin, inhibit
cell wall synthesis in bacteria.
Other agents, such as chloramphenicol, tetracyclines, and streptomycin, inhibit
protein synthesis by acting on 70S ribosomes.
Ionophore and polypeptide antibiotics damage
plasma membranes.
Some agents inhibit nucleic
acid synthesis.
Agents such as sulfanilamide act as
antimetabolites by competitively inhibiting enzyme activity.
All penicillins contain a
β-lactam ring.
Natural penicillins produced by Penicillium are effective against
gram-positive cocci and spirochetes.
Penicillinases (β-lactamases) are bacterial enzymes that destroy
natural penicillins
semisynthetic penicillins are resistant to
penicillinases and have a broader spectrum of activity than natural penicillins.
Carbapenems
broad-spectrum antibiotics that inhibit cell wall synthesis.
The monobactam aztreonam affects only
gram-negative bacteria.
Cephalosporins inhibit
cell wall synthesis and are used against penicillin-resistant strains.
Polypeptides such as bacitracin inhibit
cell wall synthesis primarily in gram-positive bacteria.
Vancomycin inhibits
cell wall synthesis and may be used to kill penicillinase-producing staphylococci.
Isoniazid (INH) and ethambutol inhibit
cell wall synthesis in mycobacteria.
Chloramphenicol
inhibit protein synthesis at 70S ribosomes.
aminoglycosides
inhibit protein synthesis at 70S ribosomes.
tetracyclines
inhibit protein synthesis at 70S ribosomes.
glycylcyclines
inhibit protein synthesis at 70S ribosomes.
macrolides
inhibit protein synthesis at 70S ribosomes.
streptogramins
inhibit protein synthesis at 70S ribosomes.
oxazolidinones
inhibit protein synthesis at 70S ribosomes.
pleuromutilins
inhibit protein synthesis at 70S ribosomes.
cause damage to plasma membranes.
Lipopeptides polymyxin B and bacitracin
Rifamycin inhibits
mRNA synthesis; it’s used to treat tuberculosis.
Quinolones and fluoroquinolones inhibit
DNA gyrase.
Sulfonamides competitively inhibit
folic acid synthesis.
SMZ-TMP competitively inhibits
dihydrofolic acid synthesis.
Fungicidal drugs
Polyenes, such as nystatin and amphotericin B,
How do Polyenes, such as nystatin and amphotericin B work?
combine with plasma membrane sterols
Azoles and allylamines interfere with
with sterol synthesis and are used to treat cutaneous and systemic mycoses.
Echinocandins interfere with
fungal cell wall synthesis.
The antifungal agent flucytosine is an antimetabolite of
cytosine
Griseofulvin interferes with
eukaryotic cell division
Griseofulvin is used primarily to treat
skin infections caused by fungi.
Entry inhibitors and fusion inhibitors bind to
viral attachment and receptor sites.
Nucleoside and nucleotide analogs such as
acyclovir and zidovudine
How do antiviral drugs like acyclovir and zidovudine work?
inhibit DNA or RNA synthesis.
Inhibitors of viral enzymes prevents
viral assembly and exit.
Alpha interferons inhibit
spread of viruses to new cells.
Chloroquine used to treat
protozoan infections.
artemisinin used to treat
protozoan infections
quinacrine used to treat
protozoan infections.
diiodohydroxyquin used to treat
protozoan infections.
pentamidine used to treat
protozoan infections
metronidazole used to treat
protozoan infections.
Antihelminthic drugs include
mebendazole, praziquantel, and ivermectin.
mebendazole used to treat
anti-helminthic
praziquantel used to treat
anti-helminthic
ivermectin used to treat
anti-helminthic
Tests are used to determine which chemotherapeutic agent is most likely to
combat a specific pathogen.
Tests to guide chemotherapy are used when
susceptibility cannot be predicted or when drug resistance arises.
What happens in the kirby-bauer test?
a bacterial culture is inoculated on an agar medium, and filter paper disks impregnated with chemotherapeutic agents are overlaid on the culture.
After incubation, the diameter of the zone of inhibition is used to determine
whether the organism is sensitive, intermediate, or resistant to the drug.
Minimal inhibitory concentration (MIC)
is the lowest concentration of drug capable of preventing microbial growth; MIC can be estimated using the E test.
Explain the broth dilution test
the microorganism is grown in liquid media containing different concentrations of a chemotherapeutic agent
minimum bactericidal concentration (MBC).
lowest concentration of a chemotherapeutic agent that kills bacteria
Many bacterial diseases, previously treatable with antibiotics, have become
resistant to antibiotics.
Superbugs
bacteria that are resistant to several antibiotics.
Drug resistance factors are transferred
horizontally between bacteria.
Horizontal gene transfer
Transfer of genes between two organisms in the same generation
Resistance may be due to
- enzymatic destruction of a drug
- prevention of penetration of the drug to its target site
- cellular or metabolic changes at target sites
- alteration of the target site
- rapid efflux of the antibiotic.
What can minimize resistance?
The discriminating use of drugs in appropriate concentrations and dosages
Antibiotic safety
The risk (e.g., side effects) versus the benefit (e.g., curing an infection) must be evaluated before antibiotics are used.
Some combinations of drugs are synergistic
they are more effective when taken together.
Some combinations of drugs are antagonistic
when taken together, both drugs become less effective than when taken alone.
Future of Chemotherapeutic Agents
New agents include antimicrobial peptides, bacteriocins, and bacteriophages
may provide new targets
Virulence factors rather than cell growth factors
zone of inhibition
The area of no bacterial growth around an antimicrobial agent in the disk-diffusion method.
superinfection
The growth of a pathogen that has developed resistance to an antimicrobial drug being used; the growth of an opportunistic pathogen.
selective toxicity
The property of some antimicrobial agents to be toxic for a microorganism and nontoxic for the host.
persister cells
Bacterial cells in a population that avoid being killed by antibiotics because they are dormant, not because they are mutants.
non-nucleoside inhibitor
A drug that binds with and inhibits the action of the HIV reverse transcriptase enzyme.
minimal inhibitory concentration (MIC)
The lowest concentration of a chemotherapeutic agent that will prevent growth of the test microorganisms.
minimal bactericidal concentration (MBC)
The lowest concentration of chemotherapeutic agent that will kill test microorganisms.
macrolide
An antibiotic that inhibits protein synthesis; for example, erythromycin.
ketolide
Semisynthetic macrolide antibiotic; effective against macrolide-resistant bacteria
E test
An agar diffusion test to determine antibiotic sensitivity using a plastic strip impregnated with varying concentrations of an antibiotic.
disk-diffusion method
An agar-diffusion test to determine microbial susceptibility to chemotherapeutic agents; also called Kirby-Bauer test.
chemotherapy
Treatment of disease with chemical substances.
carbapenems
Antibiotics that contain a β-lactam antibiotic and cilastatin.
A method of determining the minimal inhibitory concentration by using serial dilutions of an antimicrobial drug.
broth dilution test
An antibiotic that is effective against a wide range of both gram-positive and gram-negative bacteria
broad-spectrum antibiotic
A treatment capable of inhibiting bacterial growth.
bacteriostasis
A substance capable of killing bacteria.
bactericide
AZOLE
Antifungal agents that interfere with sterol synthesis.
antiretroviral
A drug used to treat HIV infection.
antibiotic
An antimicrobial agent, usually produced naturally by a bacterium or fungus.
antibiogram
Report of antibiotic susceptibility of a bacterium
antagonism
Active opposition; (1) When two drugs are less effective than either one alone. (2) Competition among microbes.
aminoglycoside
An antibiotic consisting of amino sugars and an aminocyclitol ring; for example, streptomycin.
allylamines
Antifungal agents that interfere with sterol synthesis.
Who developed the concept of chemotherapy to treat microbial diseases?
Paul Ehrlich
What are superbugs?
Bacteria that are resistant to several antibiotics
What is the lowest concentration of a drug capable of preventing microbial growth called?
Minimal inhibitory concentration (MIC)
Which test uses filter paper disks impregnated with chemotherapeutic agents to determine bacterial sensitivity?
Disk-diffusion test (Kirby-Bauer test)
What do nucleoside and nucleotide analogs inhibit?
DNA or RNA synthesis
What is the primary use of griseofulvin?
Treat skin infections caused by fungi
Which antifungal agent is an antimetabolite of cytosine?
Flucytosine
What is the function of azoles and allylamines in antifungal treatment?
Interfere with sterol synthesis
Which antifungal drugs combine with plasma membrane sterols and are fungicidal?
Polyenes
What do sulfonamides competitively inhibit?
Folic acid synthesis
What is phage therapy?
Using bacteriophages to kill bacterial cells
What is squalamine?
A steroid with antimicrobial properties isolated from sharks
What are magainins?
Antimicrobial peptides from amphibian skin glands
What is a promising new avenue of research for developing new antibiotics?
Knowledge of the basic genetic structure of microbes
What percentage of bacterial species found in nature are incapable of being grown on conventional laboratory media?
Over 99%
What makes gram-negative bacteria resistant to most antibiotics?
Their cell wall
Why do most drugs fail when tested against dormant cells?
They are tested against exponentially growing pathogens
What is one potential target for new antimicrobial drugs?
Sequestering iron
Why is there a concern about a post-antibiotic era?
Pathogens are developing resistance to current chemotherapeutic agents
What is a new approach to controlling pathogens mentioned in the text?
Targeting their virulence factors
How does tetracycline interfere with the action of penicillin?
Tetracycline stops the growth of bacteria, which interferes with penicillin’s requirement for bacterial growth
What is an example of antagonism in drug treatment?
Penicillin and tetracycline
What is antagonism in the context of drug interactions?
The simultaneous use of two drugs is less effective than when either drug is used alone
How does penicillin enhance the effectiveness of streptomycin in treating bacterial endocarditis?
Penicillin damages bacterial cell walls, making it easier for streptomycin to enter
What is an example of synergism in drug treatment?
Penicillin and streptomycin
What is synergism in the context of drug interactions?
The chemotherapeutic effect of two drugs given simultaneously is greater than the effect of either given alone
What is a possible hypersensitivity reaction to penicillins?
Allergic reaction
What should a pregnant woman consider when taking antibiotics?
Only take antibiotics classified by the FDA as presenting no evidence of risk to the fetus
What kind of damage can potentially be caused by serious side effects of antibiotics?
Liver or kidney damage
Which antibiotic is known to neutralize the effectiveness of contraceptive pills?
Rifampin
What is the term for assessing the risks against the benefits of administering a drug?
Therapeutic index
What is the recommended practice for patients to prevent antibiotic resistance?
Finish the full regimen of their antibiotic prescriptions
What is the role of β-lactamase enzymes in antibiotic resistance?
They hydrolyze the β-lactam ring of antibiotics
What is a common method to prevent the formation of antibiotic aerosols during injection?
Inserting the needle into sterile cotton to expel air bubbles
Which structure in bacteria restricts absorption of many molecules, contributing to antibiotic resistance?
Porins
What is one major mechanism by which bacteria become resistant to antibiotics?
Enzymatic destruction or inactivation of the drug
What practice in the developed world contributes significantly to antibiotic resistance?
Using antibiotics in animal feeds to promote growth
What percentage of antibiotics in rural Bangladesh were prescribed by a physician?
8%
What is the primary cause of antibiotic misuse in less-developed areas?
Antibiotics can be purchased without prescriptions
How are antibiotic resistance genes commonly spread among bacteria?
Horizontally by conjugation or transduction
What term is used for bacteria that survive antibiotic treatment due to genetic characteristics?
Persister cells
What is the purpose of antibiograms prepared by hospital personnel?
To record the susceptibility of organisms encountered clinically
What additional information can a broth dilution test provide that the diffusion method cannot?
Whether a drug is bactericidal
What is determined by making a sequence of decreasing concentrations of the drug in a broth?
Minimal inhibitory concentration (MIC)
An antimicrobial drug that inhibits peptidoglycan synthesis is most likely to be effective against
Gram positive bacteria
Bacterial infections are easier to treat using chemotherapy because
Bacteria are prokaryotic, many differences between cell types. Affect prokaryotic cells, but not human cells.
When do Superinfections occur
1.Pathogen develops resistance to the drug being used
2.Normally resistant microbiota multiply excessively
A disadvantage of using broad spectrum antibiotics for treating bacterial infections is the potential for
Superinfection
Clindamycin binds to which ribosomal subunit to inhibit translocation?
50s
Clindamycin stops
Translation in prokaryotes
Which antibiotic has noted association Clostridium difficile associated diarrhea?
Clindamycin
Which antibiotic: It’s effectiveness against anaerobes has led to its use in the treatment of acne
Clindamycin
Sulfa drugs block the cell’s ability to
synthesize essential metabolites
Anthelmintic drug that causes paralysis of the worm
Ivermectin
Results in paralysis and death of the helminth without affecting mammalian host
Ivermectin
Example of broad spectrum antihelmintic
Ivermectin
